Analysis of TNF-β, IL-10, and IL-1 Cluster Gene Polymorphisms and Clinical Risk Factors on Acute Renal Graft Rejection

Abstract

Introduction: There is growing evidence of the genetic association between certain cytokine and acute renal graft rejection. We sought to investigate the role of recipients’ TNF-β, IL-10, IL-1β and IL-1 receptor antagonist (ra) gene polymorphism as well as other variables such as PRA levels and HLA mismatches in acute renal graft rejection. Methods: TNF-β (+252A/G), IL-10(-592A/C), IL-1β (-511C/T) and IL-1ra (86bp VNTR) gene polymorphisms were determined in 157 renal allograft recipients with and without acute rejection using PCR. TNF-β, IL-10, IL-1β and IL-1ra genotypic variants were investigated for correlation with acute rejection within the first year after renal transplantation. Results: Patients with increased panel-reactive antibody (PRA) levels were predisposed to acute renal graft rejection (P=0.001). After adjusting for all variables of P 10% remained significant risk factor in a multivariate logistic regression analysis (OR=5.897, 95% confidence intervals=1.884-18.456, P=0.002). No significant difference was found between recipients with and without acute rejection regarding TNF β, IL-10, IL-1β and IL-1ra gene polymorphisms. Conclusion: Increased PRA levels have more significant impacts than cytokine gene polymorphisms on the likelihood of developing acute renal graft rejection. We should take necessary pre-transplant and/or post-transplant measures such as plasma exchange or immune adsorption to lower the PRA levels. To identify the actual role of both PRA levels and gene polymorphisms in acute renal graft rejection additional studies with larger sample sizes will be necessary.